The objectives of this study are to ascertain the quantitative and qualitative role of testosterone and estradiol, the two testicular sex steroids, in regulating secretion of pituitary FSH and LH in the male. This project represents a continuum of studies performed since 1970 involving experiments in the rat, monkey and man. Most recently, studies in the castrated male rat demonstrated that 1) testosterone administered alone at physiological doses can maintain both gonadotropins within the normal range, 2) that estradiol alone preferentially suppressed LH, but not FSH concentration and 3) that a selective increase in plasma FSH is produced when there is reduced androgen production in association with increased estradiol production. Similar changes are seen in the pituitary content of FSH and LH suggesting that these altered sex steroid levels effect gonadotropin synthesis, storage and release. These data provide an alternate explanation for the inhibin hypothesis which suggests that there is a specific non sex steroid inhibitor of FSH secretion arising from the seminiferous tubules. Estimation of the testosterone production rate (PRT) in men with germinal aplasia and increased serum FSH shows that PRT is reduced 50% despite the fact that plasma T concentration is within the normal range, indicating that in man Leydig cell function is decreased when FSH is elevated; data similar to that in the rat. Progress this year has also centered on in-vitro studies of gonadotropin synthesis where we have been able to demonstrate both incresed LH synthesis and secretion in castrate rat pituitary homogenates as well as to show precursor/product relationships of LH Alpha and Beta subunits.